The objective is to investigate the interactions of opiates, endogenous opiate-like peptides (Endorphins), and opiate antagonists with single neurons of suspected central nervous system (CNS) pain pathways. Opiates are thought to directy suppress pain transmission through the spinal cord dorsal horn. Additionally, there may be an indirect suppression by increased descending inhibition from the brain stem. Recently, a direct suppressive effect on brain stem neurons involved in relaying noxious information to the thalamus has been demonstrated (The Pharmacologist, 18: l77, l976). Also, opiate receptors and endorphins have been identified and localized in this area. Drug interactions will be approached by recording single nerve cell firing rate with microelectrodes stereotaxically placed in the following CNS structures: spinal cord dorsal horn, brain stem nuclues gigantocellularis, and mesencephalic periaqueductal gray. Single neurons will be identified as belonging to pain pathways by applying a noxious, electrical stimulus to peripheral nerves. Neurons in the pain pathways are characterized by their prolonged after-discharges following stiumlation, "wind-up" phenomenon with repeated stimulation, and unresponsiveness to non-noxious stimulation. The characteristic firing rates, interspike-interval histograms, and post-stimulus-time (PST) histograms can be quantified and statistically described and compared to adequately assess drug effects on the neuronal code for pain. Drug effects will be studied following both general I.V. infusion and direct microiontophoretic application around the single neuron. The results will be used to quantify opiate and endorphin alterations of the neuronal code for pain used by CNS neurons.